Secretory protein expression is the expression of a protein in a host cell, where the protein is exported trough the cell membrane for its release into the extracellular medium or its displayed on the cell surface, anchored to the cell membrane. Secretory protein expression is mediated by a signal peptide at the N-terminus of the protein, which directs the extracellular export of the polypeptide.
Usually, recombinant proteins are intracellularly produced in prokaryotic hosts. When the protein is recovered in such a procedure, the cells have to be lysed which leads to contamination of the recombinant protein with cellular content. The protein then has to be recovered from whole cell extracts in multi-step purification procedures, which is time consuming and results in poor yields. Also secreted proteins could be used for bacterial therapy where they target eukaryotic receptors on the target cells.
Secretion of recombinant proteins into the medium is a better strategy because purification of proteins from spent medium is easier and more compatible with continuous culturing.
Secretory protein expression has other uses. Examples of use for this type of protein expression include live-vaccine development, epitope mapping, biosorbent and biosensor development and the high throughput screening of protein and peptide libraries for drug discovery.
In secretion, recombinant proteins face the challenge of translocation across the complex cell envelope that consists of two lipid membranes (the inner and outer membrane) with a gel-like compartment, the periplasm, in between. This has been shown to be very difficult and the methods previously used have had low efficacy.
On the other hand, synthetic biology is based on engineering living organisms in order to exploit them in a myriad of applications ranging from biosensors and the production of biofuels to therapeutic treatments. Microorganisms have now long been used by the industry in the production of many therapeutic proteins. However, the fine tuning of a whole microorganism in terms of its genome by a synthetic biology approach opens up a way of exploiting the organism itself as a therapy or a therapeutic vehicle. One particularly exciting application is the possibility of creating bacterial factories that can live in diseased tissues and produce, display or secrete therapeutic proteins in situ.
In order to manipulate a host cell such as a bacterium and to turn it into a therapeutic vehicle, one must first have a very deep understanding about its genome, its proteome and all its metabolic processes. Currently a main bottleneck is the inability to predict with accuracy the behaviour of engineered bacteria. In order to minimize potential undesired effects in therapeutic applications, and with a goal of simplifying a very complex living system, some of the simplest bacteria are being studied as synthetic biology platforms.
Host bacteria can be engineered so that they synthesize a polypeptide of interest (POI) with therapeutic applications. With the goal of increasing the surface display to the exterior of the cell and/or their secretion to the outer medium, a series of strategies can be implemented. One of them is the coupling (fusion) in frame of the polypeptide of interest with a second peptide that promotes a variety of secretion processes within the host cell. Some peptides can drive POI's surface display in the extracellular section of the cell membrane. In this case, the POI can be used for eliciting an immune response via the display of a foreign protein to an immune system's machinery, and therefore the engineered bacteria carrying the fusion protein can be used as a vaccine. Some other peptides can drive the production and secretion of the fusion protein (POI-secretion enhancer) to the outer medium. In this latter case, the engineered bacteria can be used as a tissue delivery chassis of therapeutic proteins.
A range of references exist in the prior art that deal with peptides useful in surface displaying and secreting intended polypeptides. However, in spite of what is known in the field, there are many issues that still need to be addressed. The successful secretion of a polypeptide of interest by a host cell is still hindered by many factors such as: (a) the coupling of the secretion enhancer to the POI can alter the folding and final structure of either or both partners, with a subsequent change in their biological functions; and (b) the surface display and/or secretion yields are suboptimal in terms of real applicability for many bacterial host cells such as Mycoplasma. 
Therefore, it is desirable to provide for other peptide secretion enhancers.